The present application relates generally to the extracorporeal treatment of sample fluid, and, more particularly, to the extracorporeal photopheresis of blood, or a component thereof, using a microfluidic device.
Extracorporeal photopheresis is a form of apheresis therapy that involves light activated treatment of circulating blood cells outside the body. This modality is directed to circulating leukocytes (i.e., white blood cells) and has been applied to the relatively rare neoplasm, cutaneous T-cell lymphoma (CTCL). The modality involves systemic administration of a light-activatable drug, 8-methoxypsoralen, also referred to as psoralen. The drug binds to the DNA of leukocytes, whereas erythrocytes (i.e., red blood cells) and platelets, which both contain no DNA, are unaffected by the drug. A unit of blood (˜500 ml) is removed from circulation within the body via an intravenous (IV) line placed in a patient. Using a centrifuge, the leukocytes are separated from the other components of the blood and irradiated. This separation is necessary because the vastly greater number of erythrocytes would shield the leukocytes if whole blood were directly irradiated. Also, it can be undesirable to irradiate the erythrocytes for certain treatments.
The leukocytes can be irradiated with ultra-violet (UV) light at approximately 340 nm. The leukocytes are then recombined with the blood and returned to the body. The UV light causes a reaction of the psoralen to cross-link the DNA of the leukocytes and thereby damage the genetic information of the cell. The damaged cells induce an immune response that can result in the suppression of malignant T-cell production.
The above-discussed technique involves the removal of a unit of blood of ˜500 ml for processing at any one time. To treat a sufficient blood volume for an effective response, many cycles of exsanguination and reinfusion over a period of a couple days are typically necessary. However, this extended treatment duration may not be optimal for a desired immune response. Further, such systems can require precise controls for the separation, irradiation, and reintroduction of leukocytes. Applications to additional modalities have thus been impeded by the expense, size, technical demands and inconvenience to the patient imposed by equipment for extracorporeal photopheresis.